Our principal objective is to determine the interrelationship of C- type RNA viruses to autoimmune disease and neoplasia. New Zealand Black (NZB) mice offer an excellent animal model system for this study; they have a disease syndrome similar to lupus erythematosus in man and develop reticulum cell sarcomas late in life. In this investigation three areas of research are proposed: 1. We have isolated a C-type virus from NZB mice which, because it can be propagated only in cells foreign to the host species, has been called a xenotropic (X-tropic) virus. Since similar viruses have been recovered from other mice, it is probably a universal endogenous virus of mice. We want to know the mechanism by which the presence of this virus is regulated in NZB and other mouse cells and whether its increased expression in NZB mice is related to their autoimmune disease and neoplasia. We shall study the role of the host response to this virus since high titered anti-viral antibodies have been found in NZB as well as other mice. 2. Supernatants from cultured NZB cells contain an inhibitor of C-type viruses. We shall study the biologic and chemical properties of this "inhibitor" and determine its relationship to the resistance of mouse cells to X-tropic virus and the general resistance of the host to C-type virus infection. 3. Since viruses associated with other diseases characterized by circulating immune complexes replicate efficiently in macrophages, we are studying these cells as possible causes of the immune disorders in NZB mice. Graft vs. host reactions and macrophage function tests are planned using both fresh and established lines (SV40-transformed) of mouse macrophages. Finally, the knowledge gained by these studies will be utilized where possible to studies of similar diseases in man.